Dose–Response Characteristics of the Alcohol Biomarker Phosphatidylethanol (PEth)—A Study of Outpatients in Treatment for Reduced Drinking

Abstract

Aim Measurement of whole-blood phosphatidylethanol (PEth) offers high sensitivity and specificity as alcohol biomarker. A remaining issue of importance for the routine application is to better establish the relationship between PEth concentration and amount and duration of drinking. Methods The study included 36 subjects (32–83 years) voluntarily attending outpatient treatment for reduced drinking. At ~ 3- to 4-week intervals, they provided a diary on their daily alcohol intake and gave blood samples for measurement of PEth and carbohydrate-deficient transferrin (CDT). Whole-blood PEth 16:0/18:1 was measured by liquid chromatography-tandem mass spectrometry and serum CDT (%disialotransferrin) by high-performance liquid chromatography. Results At start, the self-reported past 2-week alcohol intake ranged 0–1260 (median 330) g ethanol, the PEth 16:0/18:1 concentration ranged 0.05–1.20 (median 0.23) μmol/L, and the CDT value ranged 0.7–13.0% (median 1.5%). At the final sampling after 5–20 (median 12) weeks, neither reported alcohol intake nor PEth and CDT levels differed significantly from the starting values. The PEth concentration showed best association with past 2-week drinking, followed by for intake in the next last week. The changes in PEth concentration vs past 2-week alcohol intake between two successive tests revealed that an increased ethanol intake by ~ 20 g/day elevated the PEth concentration by on average ~ 0.10 μmol/L, and vice versa for decreased drinking. Conclusions The PEth concentration correlated well with past weeks alcohol intake, albeit with a large inter-individual scatter. This indicates that it is possible to make only approximate estimates of drinking based on a single PEth value, implying risk for misclassification between moderate and heavy drinking.

Secondary Analysis of a Randomized Clinical Trial of Naltrexone Among Women Living With HIV: Correlations Between Reductions in Self‐Reported Alcohol Use and Changes in Phosphatidylethanol

“…The correlation between change in drinks per week and change in PEth was weak, which is inconsistent with Helander and colleagues (2019b) findings, which found a stronger relationship ( r = 0.46, p = <0.01) between change in number of drinks and PEth. However, between baseline and 2 months, we did find a similarly strong correlation between change in PEth and change in alcohol use among persons without an AUD, though this relationship was only apparent for relative change, not absolute change.…”

“…PEth, a phospholipid metabolite formed on the surface of red blood cells in the presence of ethanol, is a direct biomarker that offers a promising capability to detect recent alcohol use (i.e., past 2 to 3 weeks; Hahn et al, 2016a). PEth has been shown to be more sensitive and specific than other medium‐term alcohol biomarkers (i.e., biomarkers that are present for weeks to months, e.g., alanine transaminase [ALT] and aspartate transaminase [AST]; Hahn et al, 2012, 2016a; Helander et al, 2019a, 2019b; Litten et al, 2010). However, identifying a specific period of abstinence that produces a negative PEth result and the amount of alcohol that produces a positive PEth result has been hindered by the observed substantial individual differences in formation and elimination of the biomarker, thus limiting its clinical applicability (Aradottir et al, 2006; Helander et al, 2019a, 2019b; Stewart et al, 2014; Ulwelling and Smith, 2018).…”

“…In order to study whether PEth changes over time relative to changes in self‐reported alcohol use, we also need to consider other individual factors that can influence PEth. In addition to timing and patterns of alcohol use that impact the detection of PEth (Hahn et al, 2012; Helander et al, 2019b), individual differences in alcohol metabolism may also be a critical factor affecting PEth levels, as the rate of alcohol absorption in the small intestine varies across individuals (Hahn et al, 2016a; Javors et al, 2016). Such factors include age, sex, race, percent body fat, alcohol use disorders (AUD), HIV, and genetically determined levels of alcohol and acetaldehyde dehydrogenase (Hahn et al, 2016a; Javors et al, 2016; Jorgenson et al, 2017; Meier and Seitz, 2008; Zakhari and Li, 2007).…”

Performance of PEth Compared With Other Alcohol Biomarkers in Subjects Presenting For Occupational and Pre-Employment Medical Examination

“…A recent study from our group also supported the use of 0.30 μmol/L as the cut-off to indicate harmful drinking (>50 g/day) ( Helander et al , 2019 ). This limit is to be considered as safe and allows the interpretation of chronic high alcohol intake even when considering the inter-individual variability in PEth response to alcohol exposure ( Helander et al , 2019b ).…”

Growing potential and remaining uncertainties in assessing prenatal alcohol exposure in dry blood spots

“…With the range of positive PEth values reported between the LOD and 346 ng/ml and a mean of 20.7 ng/ml (median was not reported), it would be interesting to see the differences in patient characteristics by PEth concentration quartiles. Attempts have been made to approximate quantity of alcohol consumption based on PEth value in liquid blood; however, differentiation between moderate and heavy drinking was challenging ( 7 ), and the utility of PEth to quantify lower levels of consumption is not well characterized.…”